Potent and Selective Inhibitors of CDPK1 from T. gondii and C. parvum Based on a 5‑Aminopyrazole-4-carboxamide
Scaffold

Zhang, Zhongsheng; Ojo, Kayode
K.; Vidadala, RamaSubbaRao; Huang, Wenlin; Geiger, Jennifer A.; Scheele, Suzanne; Choi, Ryan; Reid, Molly C.; Keyloun, Katelyn R.; Rivas, Kasey; Siddaramaiah, Latha Kallur; Comess, Kenneth M.; Robinson, Kenneth P.; Merta, Philip J.; Kifle, Lemma; G. J. Hol, Wim; Parsons, Marilyn; Merritt, Ethan A.; Maly, Dustin J.; L. M. J. Verlinde, Christophe; C. Van Voorhis, Wesley; Fan, Erkang

doi:10.1021/ml400315s.s001

ml400315s_si_001.pdf (326.89 kB)

Potent and Selective Inhibitors of CDPK1 from T. gondii and C. parvum Based on a 5‑Aminopyrazole-4-carboxamide Scaffold

journal contribution

posted on 2014-01-09, 00:00 authored by Zhongsheng Zhang, Kayode K. Ojo, RamaSubbaRao Vidadala, Wenlin Huang, Jennifer A. Geiger, Suzanne Scheele, Ryan Choi, Molly C. Reid, Katelyn R. Keyloun, Kasey Rivas, Latha Kallur Siddaramaiah, Kenneth M. Comess, Kenneth P. Robinson, Philip J. Merta, Lemma Kifle, Wim G. J. Hol, Marilyn Parsons, Ethan A. Merritt, Dustin J. Maly, Christophe L. M. J. Verlinde, Wesley C. Van Voorhis, Erkang Fan

5-Aminopyrazole-4-carboxamide was used as an alternative scaffold to substitute for the pyrazolopyrimidine of a known “bumped kinase inhibitor” to create selective inhibitors of calcium-dependent protein kinase-1 from both Toxoplasma gondii and Cryptosporidium parvum. Compounds with low nanomolar inhibitory potencies against the target enzymes were obtained. The most selective inhibitors also exhibited submicromolar activities in T. gondii cell proliferation assays and were shown to be nontoxic to mammalian cells.